Association of caspase-8 mutation with chemoresistance to cisplatin in HOC313 head and neck squamous cell carcinoma cells.
Biochem Biophys Res Commun
; 390(3): 989-94, 2009 Dec 18.
Article
em En
| MEDLINE
| ID: mdl-19852930
ABSTRACT
Caspase-8 is a critical upstream mediator of apoptosis in the death receptor pathway. However, the relationship between caspase-8 mutation and chemosensitivity remain unclear in head and neck squamous cell carcinoma (HNSCC) carrying p53 mutation. In this study, we identified a caspase-8 nonsense mutation, accompanied by the loss of the second allele, in a drug-resistant HOC313 HNSCC cell line. The nonsense mutation (R68X) leads to truncation of all defined functional domains. Reconstitution of caspase-8 by stable transfection of wild-type caspase-8 sensitized the cells to cisplatin-, but not etoposide-induced apoptosis. Consistent with this, cisplatin, but not etoposide, induced TNF-alpha and TRAIL mRNA in caspase-8 reconstituted HOC313 cells, accompanied by activation of the reconstituted caspase-8 and its downstream caspase-3. These results indicate that the loss of caspase-8 plays an important role in acquisition of chemoresistance to cisplatin in HOC313 cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Escamosas
/
Cisplatino
/
Resistencia a Medicamentos Antineoplásicos
/
Caspase 8
/
Neoplasias de Cabeça e Pescoço
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Antineoplásicos
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão